不同剂量米氮平联合草酸艾司西酞普兰治疗抑郁症伴焦虑临床疗效和安全性的Meta-分析

A Meta-Analysis of Clinical Efficacy and Safety of Mirtazapine in Different Doses Combined with Escitalopram Oxalate in the Treatment of Depression with Anxiety

摘要: 目的：系统评价大剂量(30 mg/d)米氮平与小剂量(15 mg/d)联合常规剂量草酸艾司西酞普兰对抑郁症伴焦虑的临床疗效和安全性，寻找米氮平的合适剂量，为临床选择提供依据。方法：计算机检索PubMed、Cochrane library、Embase、中国生物医学文献数据库(CBMdisc/SinoMed)、中国期刊全文数据库(CNIK)、维普数据库(VIP)、万方数据库，收集有关不同剂量米氮平联合草酸艾司西酞普兰片治疗抑郁伴焦虑或抑郁症的临床随机对照试验(RCT)，检索时限为建库至2020年8月。由两名研究者独立筛选文献并提取数据后，应用RevMan 5.3软件进行Meta-分析。结果：纳入11项RCTs，共涉及878例患者。Meta-分析结果显示：① 到达治疗周期终点时，大剂量组的总有效率(RR = 1.20, 95% CI = 1.13~1.26, P < 0.00001)和痊愈率(RR = 1.52, 95% CI = 1.22~1.88, P = 0.0002)都明显高于小剂量组；② 治疗2，4，8周后HAMD评分大剂量组与小剂量组的差异存在明显的统计学意义(2周：MD = −5.57，95% CI = −6.04~−5.10，P < 0.00001；4周：MD = −4.78，95% CI = −5.19~−4.37，P < 0.00001；8周：MD = −4.23，95% CI = −4.83~−3.62，P < 0.00001)；治疗8周后两组的HAMA评分差异不具有统计学意义(P = 0.12)；③ 到达治疗终点时，大剂量组的总不良反应发生率高于低剂量组(RR = 1.30，95% CI = 1.08~1.55，P = 0.005)，在常见的不良反应中，导致体重增加的发生率两组之间差异具有统计学意义(RR = 2.66，95% CI = 1.48~4.75，P = 0.001)，两组其余不良反应差异不具有统计学意义(P > 0.05)。结论：对于抑郁症伴焦虑患者，大剂量(30 mg/d)米氮平联合常规剂量的草酸艾司西酞普兰临床疗效优于小剂量(15 mg/d)，但由于大剂量组用药安全性较低，结合其他研究的结果，建议选择小剂量米氮平进行联合治疗以保证用药安全性。

Abstract: Objective: To systematically evaluate the efficacy and safety of high dose (30 mg/d) mirtazapine and low dose (15 mg/d) combined with conventional dose of escitalopram oxalate in the treatment of depression and anxiety, and to find an appropriate dose of mirtazapine, so as to provide an evidence for clinical selection. Methods: A systematic literature search was conducted in English and Chinese database of PubMed, the Cochrane library, Embase, China Biology Medicine disc (CBMdisc/SinoMed), China National Knowledge Infrastructure Database (CNKI), VIP and WanFang. Relevant randomized controlled trials (RCTs) about doses of mirtazapine in combination of escitalopram oxalate citalopram tablets in the treatment of depression with anxiety or depression was collected, limited in the time from building the library to August 2020. After the articles were screened while the data was extracted by two researchers independently, the RevMan 5.3 software was used for Meta-analysis. Results: ① Eleven RCTs were included, involving a total of 878 patients. The results of meta-analysis showed that the total effective rate (RR = 1.20, 95% CI = 1.13 - 1.26, P < 0.00001) and recovery rate (RR = 1.52, 95% CI = 1.22 - 1.88, P = 0.0002) of the high-dose group were significantly higher than those of the low-dose group at the end of the treatment cycle. ② After 2, 4, and 8 weeks of treatment, the HAMD score showed statistically significant differences between the high-dose group and the low-dose group (2 weeks: MD = −5.57, 95% CI = −6.04 - −5.10, P < 0.00001). 4 weeks: MD = −4.78, 95% CI = −5.19 - −4.37, P < 0.00001; 8 weeks: MD = −4.23, 95% CI = −4.83 - −3.62, P < 0.00001); HAMA score difference between the two groups after 8 weeks of treatment was not statistically significant (P = 0.12). ③ In the end of treatment, the total incidence of adverse reactions of high-dose group was higher than low dose group (RR = 1.30, 95% CI = 1.08 - 1.55, P = 0.005). Among common adverse reactions, the incidence of weight gain had a statistically significant difference between the two groups (RR = 2.66, 95% CI = 1.48 - 4.75, P = 0.001), and the rest of the adverse reactions between the two groups have no statistical significance (P > 0.05). Conclusion: The efficacy of the large dose (30 mg/d) of mirtazapine combined with conventional dose of escitalopram oxalate citalopram was better than that of small dose (15 mg/d). But due to the low drug safety of high-dose group, it is recommended to choose low-dose mirtazapine as a combination therapy to ensure the drug safety.